Faster Time-to-Therapeutic Tacrolimus Level is Associated with Lower Risk of Cellular Rejection Early after Heart Transplantation

Abstract

Faster time-to-therapeutic tacrolimus (TTT) levels is associated with lower rates of acute cellular rejection (ACR) in kidney and liver transplantation. Limited data have evaluated this relationship in heart transplant (HT) recipients. Single-center retrospective chart review of patients who received HT from January 1, 2014 to June 30, 2016. Multi-organ transplant recipients, re-transplants, and those who received induction therapy with either basiliximab or thymoglobulin were excluded. A therapeutic tacrolimus concentration was defined as a trough level between 8-15 ng/mL for two consecutive days. The primary outcome was the rates of 30-day ACR in patients who were < and ≥ the median TTT level. Serum creatinine values were also collected for the first 10 post-op days. From a database of 88 HT patients we evaluated 55 patients who did not receive induction therapy (median age=56 (49-65), 73% white, 71% had a VAD prior to HT). The median TTT level was 9 days; patients < the median (n=25) had similar characteristics as those ≥ the median (n=30). Rates of ACR were significantly lower in the < median group (8 v. 43%, p=0.005) (Figure), while serum creatinine values were similar between groups (p>0.05 for each day). Patients without ACR (n=40) had a median TTT level of 8 (6-9.5) days, compared to 10 (9-12) days in the ACR group (n=15) (p=0.01). A multivariate regression model found TTT ≥9 days to be significantly associated with early ACR after adjusting for age, gender, and VAD pre-HT (OR 9.84, 95% CI [1.86-52.90], p=0.007). Quickly achieving a TTT level reduces the risk of ACR early after HT without adversely affecting renal function.